A Multi-center, Randomized, Double-blind, Placebo Control Phase 1b/II Study to Evaluate the Safety and Efficacy of IMC-002 for the Treatment of Active Systemic Lupus Erythematosus

The purpose of this study is to evaluate the efficacy and safety of IMC-002 in the treatment of active SLE.

Start Date10 Oct 2024

Sponsor / Collaborator

ImmuneCare Biopharmaceuticals (Shanghai) Co., Ltd.

NCT06557174 / Not yet recruitingPhase 1/2

A Phase Ib/III Multi-center, Randomized and Positive Control Study to Evaluate IMC-002 Safety and Efficacy in in Neuromyelitis Optica Spectrum Disorder (NMOSD) Patients

The purpose of this study is to evaluate the efficacy and safety of IMC-002 in the treatment of NMOSD.

Start Date10 Oct 2024

Sponsor / Collaborator

ImmuneCare Biopharmaceuticals (Shanghai) Co., Ltd.

CTR20231000 / RecruitingPhase 1/2

注射用IMM0306联合来那度胺治疗复发/难治CD20阳性B细胞非霍奇金淋巴瘤的Ib/Ⅱa 期临床研究

[Translation] Phase Ib/Ⅱa clinical study of IMM0306 for injection combined with lenalidomide in the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin's lymphoma

Ib期：剂量递增阶段：评估IMM0306与来那度胺联合用药的安全性和耐受性，确定最大耐受剂量（MTD）（如有）和推荐2期剂量（RP2D）；初步评估IMM0306与来那度胺联合用药的抗肿瘤疗效；评估IMM0306与来那度胺联合用药的免疫原性；评估IMM0306与来那度胺联合用药的药代动力学（PK）特征；探索IMM0306的暴露与疗效、安全性的相关性（如数据允许）；探索生物标志物与安全性的相关性；探索淋巴细胞亚群变化与疗效相关性； IIa期：队列扩展阶段评估IMM0306与来那度胺联合用药的抗肿瘤疗效；进一步评估IMM0306与来那度胺联合用药的抗肿瘤疗效；进一步评估IMM0306与来那度胺联合用药的安全性和耐受性；注射用IMM0306与来那度胺联合用药在CD20阳性B-NHL受试者中的免疫原性；基于群体PK分析方法，表征IMM0306在晚期实体瘤受试者中的PK特征（如数据允许）；探索IMM0306的暴露与疗效、安全性之间的相关性（如数据允许）。

[Translation]

Phase Ib: Dose escalation phase: Evaluate the safety and tolerability of IMM0306 combined with lenalidomide, determine the maximum tolerated dose (MTD) (if any) and the recommended phase 2 dose (RP2D); preliminarily evaluate the anti-tumor efficacy of IMM0306 combined with lenalidomide; evaluate the immunogenicity of IMM0306 combined with lenalidomide; evaluate the pharmacokinetic (PK) characteristics of IMM0306 combined with lenalidomide; explore the correlation between IMM0306 exposure and efficacy and safety (if data permits); explore the correlation between biomarkers and safety; explore the correlation between changes in lymphocyte subsets and efficacy; Phase IIa: Cohort expansion phase To evaluate the anti-tumor efficacy of IMM0306 in combination with lenalidomide; to further evaluate the anti-tumor efficacy of IMM0306 in combination with lenalidomide; to further evaluate the safety and tolerability of IMM0306 in combination with lenalidomide; to evaluate the immunogenicity of IMM0306 for injection in combination with lenalidomide in subjects with CD20-positive B-NHL; to characterize the PK characteristics of IMM0306 in subjects with advanced solid tumors based on population PK analysis methods (if data permit); to explore the correlation between the exposure of IMM0306 and its efficacy and safety (if data permit).

Start Date07 Jun 2023

Sponsor / Collaborator

ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup

100 Clinical Results associated with Amulirafusp alfa

100 Translational Medicine associated with Amulirafusp alfa

100 Patents (Medical) associated with Amulirafusp alfa

Literatures (Medical) associated with Amulirafusp alfa

01 Mar 2023·Leukemia

IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement by simultaneously binding to CD47 and CD20 of B cells

Letter

Author: Song, Yongping ; Jiang, Zhongxing ; Zhao, Gui ; Tian, Wenzhi ; Chen, Dianze ; Zhang, Li ; Guo, Huiqin ; Bai, Xing ; Yu, Jifeng ; Yang, Chunmei ; Li, Song ; Liu, Sijin ; Peng, Liang ; Zhang, Ruliang ; Liu, Dandan ; Zhang, Wei ; Tu, Xiaoping

CD47, as the 'don't eat me' signal, interacts with the inhibitory signal-regulatory protein alpha (SIRPα) receptor expressed by myeloid cells and activated NK cells and is overexpressed in different malignancies, causing tumors to escape the phagocytosis of macrophages.Here, we describe the antitumor mechanism of IMM0306, a fusion protein of CD20 monoclonal antibody (mAb) with the CD47 binding domain of SIRPα , by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcγR engagement by simultaneously binding to CD47 and CD20 of B cells in different mouse xenograft tumor models.IMM0306 is a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα on both heavy chains, that was constructed and produced using an inhouse developed CHO-K1 cell expression system; whose binding activity was analyzed by flow cytometry.The phagocytosis and in vitro anti-tumor activity of IMM0306 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays.The ADCC assay showed that IMM0306 has strong ADCC induced by activating NK cells through enhanced Fc/ FcγRRIIIa interaction.In conclusion, our data demonstrated that IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα , exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcγR engagement by simultaneously binding to CD47 and CD20 of B cells.We conclude the mechanism of action of IMM0306 by blocking the CD47 'don't eat me' signal and activating the Fc-receptor 'eat me' signal of CD20 with a strong ADCP to make the B-cell fully killed, whereas CD47 mAbs and rituximab can only either block the CD47 'don't eat me' signal or activate the Fc-receptor 'eat me' signal of CD20 with limited ADCP to make the limited B-cell killed.The Fc segment of the recombinant protein in IMM0306 is IgG1 and has been modified by ADCC-enhanced genetic engineering.Therefore, it has strong in vivo efficacy (through ADCC and ADCP).For other CD47 BsAbs, because the CD47 antibody itself combines with red blood cells, IgG1 cannot be selected; otherwise, it will have severe anemia toxicity.Therefore, this data revealed that IMM0306 has a safer profile and superior therapeutic potential than other CD47 mAbs and BsAbs.

Haematologica

Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large Bcell lymphomas and regulates the pro-tumor microenvironment

Article

Author: Hao, Mu ; Qiu, Lugui ; Wang, Yi ; Fang, Teng ; Wang, Jingya ; Guan, Xuwen ; Li, Ru

The activated B-cell–like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell–like subtype (GCB-DLBCL). Currently, targeting tumor microenvironment (TME) is the promising approach to cure DLBCL with profound molecular heterogeneity, however, the factors affecting the tumor-promoting TME of ABCDLBCL are elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABCDLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME enhancing angiogenesis, and the expression of cytokine IL-6 and IL-10, as well as decreasing T cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in coordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumorpromoting effects of IL-16,which provides new insight into treatment strategy in ABC-DLBCL.

100 Deals associated with Amulirafusp alfa

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuromyelitis Optica	Phase 2	-	ImmuneCare Biopharmaceuticals (Shanghai) Co., Ltd.	10 Oct 2024
Systemic Lupus Erythematosus	Phase 2	CN	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	12 Aug 2024
Diffuse Large B-Cell Lymphoma	Phase 2	CN	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	07 Jun 2023
Follicular Lymphoma	Phase 2	CN	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	07 Jun 2023
Mantle-Cell Lymphoma	Phase 2	CN	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	07 Jun 2023
B-Cell Lymphoma	Phase 2	-	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	01 May 2023
CD20 Positive B-Cell Non-Hodgkin Lymphoma	Phase 2	CN	ImmuneOnco Biopharmaceuticals (Shanghai), Inc.Startup	02 Mar 2020

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05771883 (ESMO2024) Manual	Phase 1	CD20 Positive B-Cell Non-Hodgkin Lymphoma CD20-positive	11	Amulirafusp alfa+lenalidomide	(awssslwnml) = Two DLTs (grade 4 PLT decreased without bleeding) were observed at 2.0 mg/kg IMM0306 + 20 mg Lenalidomide dose level. wruvixdqic (kbcpvzeejh ) View more	Positive	15 Sep 2024
NCT05805943 (ESMO2024) Manual	Phase 2	CD20 Positive B-Cell Non-Hodgkin Lymphoma	16	Amulirafusp alfa 2.0 mg/kg	(gnfimwizwy) = palpdkvanp wwqneauidk (dnfobadwjo ) View more	Positive	15 Sep 2024
NCT05805943 (phase I study of IMM0306, ASCO2024)	Phase 1	CD20 Positive B-Cell Non-Hodgkin Lymphoma	48	IMM0306 0.04 mg/kg	cifedxiweo(acqrprhqdt) = acdjzabqsn anixefciep (qrzynmoopa ) View more	Positive	24 May 2024
NCT05805943 (phase I study of IMM0306, ASCO2024)	Phase 1	CD20 Positive B-Cell Non-Hodgkin Lymphoma	48	IMM0306 0.1 mg/kg	cifedxiweo(acqrprhqdt) = exrjocglbu anixefciep (qrzynmoopa ) View more	Positive	24 May 2024
NCT05771883 (Phase I, ASCO2024)	Phase 1	CD20 Positive B-Cell Non-Hodgkin Lymphoma CD20-positive	8	IMM0306 1.6 mg/kg + Lenalidomide 20 mg	(xfwjnpwcif) = One pt experienced treatment related serious adverse event patgmtywmg (ovkcgrmlpn )	Positive	24 May 2024
NCT05805943 (AACR2024) Manual	Phase 1	CD20 Positive B-Cell Non-Hodgkin Lymphoma	48	IMM0306	(jjkuhpdsea) = The most frequent treatment related adverse events (TRAEs) were WBC decreased (66.7%), anemia (64.6%), lymphocyte decreased (58.3%), ANC decreased (47.9%), PLT decreased (45.8%), infusion-related reactions (35.4%) bttgygcdro (aljkhhdlye ) View more	Positive	05 Apr 2024
CTR20192612 (ASCO2023) Manual	Phase 1/2	CD20 Positive B-Cell Non-Hodgkin Lymphoma CD20 Expression	42	IMM0306	(ctdtngqnpt) = Three treatment related SAEs were PLT decreased (grade 4), chest pain (grade 2) and diarrhea (grade 3). ybvcatddeu (lxwcrlmczd ) View more	Positive	31 May 2023

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